Mesoporous silica nanomaterials allow different biomedical applications such as drug delivery, therapeutic imaging, and diagnosis. In this context, mesoporous silica nanoparticles (MSNPs) have been hugely studied as a vector for drug delivery applications.
Mesoporous silica micro or nanoparticles are generally synthesized using template-assisted sol-gel methods.
In order to attach different structure around those MSNPs, such as, for example, a supported lipid bilayer (SLB), it is interesting to be able to functionalize the MSNPs with a reactive moiety which is on the external surface of the MSNPs, allowing subsequently further functionalization.
Among different methods, Bein and co-workers (Chem. Mater., 2008, 20, 7207-7214) have reported the self-assembly of MSNPs, in particular functionalized MSNPs. The self-assembly is provided by mixing a surfactant, which is employed as structure-directing agent, a silica precursor, and an organotriethoxysilane, which will provide the functional moiety onto the external surface of the nanoparticles, in an alkaline aqueous media containing a polyalcohol, which is going to slow down the condensation rate of the silica species.
The surfactant is cetyltrimethylammonium chloride (CTACl).
The silica precursor is tetraethylorthosilicate (TEOS).
The organotriethoxysilane is 3-aminopropyltriethoxysilane (APTES). It can also be, for example, phenyltriethoxysilane (PTES).
The polyalcohol is triethanolamine (TEA).
The protocol provided by the Bein's research group requires the co-condensation of all of the above mentioned reagents to provide the self-assembly of the functionalized MSNPs.
Thus, a first mixture of TEOS, CTACl, TEA in water is prepared and is co-condensed with a mixture of TEOS and the organotriethoxysilane. The second mixture, comprising TEOS and the organotriethoxysilane, always contained 185 μmol of silane, namely 2% of the total amount of silane involved in the preparation of the MSNPs.
The second mixture can be added onto the first mixture at different time, depending of the nanoparticle growth.
By using this above co-condensation principle and such ratio, non-aggregated functionalized MSNPs were obtained. However, the yield of functionalized, namely the yield of organotriethoxysilane incorporated within the external surface of the nanoparticles is dependent of the starting concentration of organotriethoxysilane, which is always below 2% of the total amount of silane involved in the preparation of the MSNPs.
The yield of the functionalization of the nanoparticles with the amino group (using subsequently APTES as organotriethoxysilane) was reported using ζ-potential measurements.
ζ-potential experiments performed after 10 or 30 minutes of particle growth at a pH of 6 indicates a ζ-potential between 0 mV and 5 mV. At more acidic pH values, the ζ-potential logically increases (up to 10 mV at a pH of 4 and up to more than 25 mV at a pH of 2 after 30 minutes of particle growth).
When the co-condensation route was not performed, namely when the organotriethoxysilane (at a concentration equal to 2% of the total amount of silane involved in the preparation of the MSNPs) was added directly (without condensation with TEOS), the final nanoparticles obtained where either aggregated (in the case where APTES was used) or non-functionalized (in the case where PTES was used).
Those results suggest that when the organotriethoxysilane is used at this concentration, the pores and the channels of the nanoparticles in formation becomes blocked. However, when co-condensation is previously performed, the organotriethoxysilanes are hydrolysed forming oligosilicate anions which can subsequently reacts with the silica wall which is built during the nanoparticle growth.